Correlations between genomic subgroup and clinical features in a cohort of more than 3000 meningiomas.

Autor:	Youngblood MW; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery.; 3Department of Genetics, and., Duran D; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery.; 4Department of Neurosurgery, University of Mississippi Medical Center, Jackson, Mississippi., Montejo JD; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery.; 5Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire., Li C; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery.; 6Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.; 7The Third Xiangya Hospital, Central South University, Changsha, China., Omay SB; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery., Özduman K; 8Department of Neurosurgery, Acibadem Mehmet Ali Aydınlar University, School of Medicine, Istanbul, Turkey., Sheth AH; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery., Zhao AY; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery., Tyrtova E; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery., Miyagishima DF; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery.; 3Department of Genetics, and., Fomchenko EI; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery., Hong CS; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery., Clark VE; 9Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts., Riche M; 10Department of Neurosurgery, Hôpital Universitaire Pitié-Salpêtrière, AP-HP & Sorbonne Université, Paris, France., Peyre M; 10Department of Neurosurgery, Hôpital Universitaire Pitié-Salpêtrière, AP-HP & Sorbonne Université, Paris, France., Boetto J; 10Department of Neurosurgery, Hôpital Universitaire Pitié-Salpêtrière, AP-HP & Sorbonne Université, Paris, France., Sohrabi S; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery., Koljaka S; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery., Baranoski JF; 11Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona., Knight J; 3Department of Genetics, and.; 12Yale Center for Genome Analysis, Yale University West Campus, Orange, Connecticut., Zhu H; 13Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China., Pamir MN; 8Department of Neurosurgery, Acibadem Mehmet Ali Aydınlar University, School of Medicine, Istanbul, Turkey., Avşar T; 14Department of Medical Biology, BAU Faculty of Medicine, Istanbul, Turkey., Kilic T; 15Department of Neurosurgery, Bahcesehir University, School of Medicine, Istanbul, Turkey., Schramm J; 16University of Bonn Medical School, Bonn, Germany., Timmer M; 17Center for Neurosurgery, University Hospital of Cologne, Germany., Goldbrunner R; 17Center for Neurosurgery, University Hospital of Cologne, Germany., Gong Y; 13Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China., Bayri Y; 18Department of Neurosurgery, Marmara University School of Medicine, Istanbul, Turkey., Amankulor N; 19Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania., Hamilton RL; 19Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania., Bilguvar K; 3Department of Genetics, and.; 12Yale Center for Genome Analysis, Yale University West Campus, Orange, Connecticut., Tikhonova I; 12Yale Center for Genome Analysis, Yale University West Campus, Orange, Connecticut., Tomak PR; 2Department of Neurosurgery., Huttner A; 1Yale Program in Brain Tumor Research.; 20Department of Pathology, Yale School of Medicine, New Haven, Connecticut and., Simon M; 16University of Bonn Medical School, Bonn, Germany.; 21Department of Neurosurgery, Bethel Clinic, Bielefeld, Germany., Krischek B; 17Center for Neurosurgery, University Hospital of Cologne, Germany., Kalamarides M; 10Department of Neurosurgery, Hôpital Universitaire Pitié-Salpêtrière, AP-HP & Sorbonne Université, Paris, France., Erson-Omay EZ; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery., Moliterno J; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery., Günel M; 1Yale Program in Brain Tumor Research.; 2Department of Neurosurgery.; 3Department of Genetics, and.; 12Yale Center for Genome Analysis, Yale University West Campus, Orange, Connecticut.; 22Department of Neuroscience, Yale School of Medicine, New Haven, Connecticut.
Jazyk:	angličtina
Zdroj:	Journal of neurosurgery [J Neurosurg] 2019 Oct 25; Vol. 133 (5), pp. 1345-1354. Date of Electronic Publication: 2019 Oct 25 (Print Publication: 2020).
DOI:	10.3171/2019.8.JNS191266
Abstrakt:	Objective: Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts. Methods: Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher's exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features. Results: Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among "mutation unknown" samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor's underlying driver mutation. Conclusions: Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.
Databáze:	MEDLINE
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